| BackgroundAtrial fibrillation (AF) is the most common cardiac arrhythmia. In recent years, many single nucleotide polymorphisms (SNPs) were improved to be associated with AF ocurrence. We aimed to investigate the associations of SNPs in candidate gene and previously GWAS reported SNPs with AF risk in Chinese Han population.MethodsIn this study,1:lcase-control study method was adopted and the subjects were 1,150 AF patients selected from Chinese Han population, matched the case group and the control group with age and gender. First part of the study, we genotyped the selected SNPs using the improved multiplex ligation detection reaction (iMLDR) technique. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression analyses to estimate the associations between SNPs and risk of AF. Next, to confirm the observed effects of rs2200733 on AF, genotyping was performed again using the TaqMan allelic discrimination assay. We also used Chi-square-based Q-test to assess the heterogeneity of associations between subgroups.ResultsA total of 2,300 Chinese Han origin individuals were enrolled including 1,150 AF patients and 1,150 non-AF controls. There were no significant differences for the distributions of age and gender between AF group and control group (for male proportion:65.8% vs.65.8%, P= 1; for age:58.66 ±11.50 years vs.59.06 ± 10.48 years, P= 0.379 and 1, respectively). The known risk factors for AF, including coronary artery disease (CAD), diabetes and hypertension were more prevalent in the AF group than in the control group. A total of 13 SNPs were selected for genotyping including 8 SNPs in previously study and 5 SNPs in PITX2. For the 8 SNPs reported by the paper, the logistic regression analyses revealed that the four SNPs (rs6584555, rs10507248, rs13216675 and rs11047543) were associated were significantly associated with AF in the additive model after controlling for covariates of gender, age, hypertension, CAD, and diabetes. There was no obvious evidence of significant associations between the other four SNPs and AF risk. We further calculated P values for false discovery rate (PFDR) to perform multiple comparisons. After multiple comparisons, the SNP rs6584555 remained significant association with the risk of AF (OR= 1.51,95% CI:1.27-1.78, P= 1.95 × 10-6, PFDR=1.56 × 10’5). However, rs10507248, rs13216675 and rs11047543 lost their associations with the risk of AF. For the five SNPs in PITX2, the logistic regression analyses revealed that the two SNPs (rs1982361 and rs2200733) were associated were significantly associated with AF in the additive model after controlling for covariates of gender, age, hypertension, CAD, and diabetes (OR= 0.75,95% CI:0.66-0.85, P= 1.10× 10-6 for rsl982361;OR= 2.10,95% CI:1.85-2.40, P= 2.53× 10-29 for rs2200733). There were no obvious evidences of significant associations between the other three loci and AF risk. We further calculated P values for false discovery rate (PFDR) to perform multiple comparisons. After comparisons, we found that the 2 SNPs still remained their associations with the risk of AF (PFDR=2.75 ×10-6, PFDR=1.26×10-28, respectively). Genotyping was performed again using the TaqMan allelic discrimination assay to confirm the observed effects of rs2200733 on AF. Finally, the association between rs2200733 and AF risk was consistently (OR=2.10,95% CI: 1.84-2.40, P= 6.59×10-29, call rate 99.7%). Moreover, in an effort to investigate the associations of rs6584555, rs1982361 and rs2200733 with AF risk in subgroups, we carried out stratification analyses based on risk factors for AF, including age, gender, hypertension and diabetes, similar effects were observed between subgroups and P values for heterogeneity were all more than 0.05. The risk factor CAD was not stratified because there were no CAD patients in control group.Conclusions1, Rs6584555 C in NEURL may contribute to the risk of AF in Chinese Han populations.2, Rs1982361 G in PITX2 was found to be significantly associated with a decreased risk of AF, while rs2200733 C was associated with an increased risk of AF. |
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